SOLUTION CONFORMATION OF AN IMMUNOGENIC PEPTIDE DERIVED FROM THE PRINCIPAL NEUTRALIZING DETERMINANT OF THE HIV-2 ENVELOPE GLYCOPROTEIN GP125

Background: The conformational preferences of a number of peptides wit h sequences related to the envelope glycoproteins of HIV-1 have been i nvestigated in the past few years. Similar studies have not been made for HIV-2, which is a distinct virus with similar physiological effect s to those of HIV-1. The discovery of common structural features would be a promising route to the design of immunogens for generally effect ive HIV vaccines. We present the results of an NMR conformational stud y of a sequence deriving from the V3 loop of HIV-2. Results: Three syn thetic immunogenic peptides were studied, of 12, 22 and 39 amino acids in length, all containing a central Met-Ser-Gly-Arg sequence conserve d among a number of HIV-2 isolates. In addition, the 39-mer contained a disulfide bond between cysteine residues close to the ends of the mo lecule, forming a loop that is thought to comprise an important struct ural and immunological component of the intact glycoprotein. All three peptides display well defined beta-turns in the Met-Ser-Gly-Arg seque nce, independent of the integrity of the disulfide bond. No other conf ormational preferences for folded conformations were found for the pep tides. Conclusions: The presence of a beta-turn in the Met-Ser-Gly-Arg sequence is strikingly similar to the behavior seen for the correspon ding principal neutralizing determinant sequence from gp120 of HIV-1 a nd argues, in the absence of information on the three-dimensional stru cture of the intact proteins, for a similarity in the structure of thi s region that could be exploited in the design of synthetic peptide va ccines generally effective against HIV infections. (C) Current Biology Ltd